RAS/RAF/MAPK and PI3K/AKT/mTOR signal transduction pathways are the most dysfunctional pathways in multiple cancer types including GC.90,91 RTKs alterations in tumors lead to activation of both MAPK and PI3K pathways, and targeting the PI3K pathway was confirmed to promote cancer progression through MAPK signals and vice versa92 (Fig. 2). The gene discussed is PIK3CA; the disease is cancer.